Support is requested for a Keystone Symposia meeting entitled The Brain: Adaptation and Maladaptation in Chronic Pain, organized by Frank Porreca, David Borsook and David W. Dodick. The meeting will be held in Keystone, Colorado from June 15 - 20, 2014. Recent genetic, epigenetic, functional imaging, and receptor pharmacology advances have revealed chronic pain as a complex disease with long-lasting functional and structural consequences in the peripheral and central nervous system. Fortunately, it has also uncovered promising molecular targets that will inform drug discovery for decades to come. The risk factors and precise mechanisms by which pain becomes chronic and persistent, the potential for structural changes to normalize, and effective strategies to eliminat chronic pain are becoming better understood, but still require a considerable and sustained effort from the scientific and clinical community. This Keystone Symposia meeting will bring together some of the world's leading scientific experts to provide an authoritative synthesis of the current state of knowledge of the biology and treatment of chronic pain, identify and prioritize important gaps in our understanding, and set strategic directions for future research which ultimately can be translated into highly specific and effective treatments to lessen the enormous burden of chronic pain in America.